The Ki67 protein is a marker used in medicine to gauge cellular proliferation. Found within the cell nucleus, its presence is linked to cell division, making it an indicator for how rapidly cells are multiplying. This is particularly valuable in oncology, where understanding a tumor’s growth rate can inform prognosis and guide treatment decisions. Ki67 has become a routine part of pathological analysis for many types of cancer.
The Role of Ki67 in Cell Division
To understand Ki67’s function, it is helpful to review the cell cycle. A cell exists in either a resting state (G0) or an active state of division. The active phases of proliferation include G1, S, G2, and M, during which the cell grows, duplicates its DNA, and splits into two daughter cells.
The Ki67 protein is produced only by cells in these active phases. Its levels rise as a cell enters the G1 phase, increase through the S and G2 phases, and peak during mitosis (M phase). Once mitosis is complete and the cell enters a new cycle or the resting G0 state, the Ki67 protein is rapidly degraded. This strict correlation to active cell division makes it a precise biomarker.
The presence of Ki67 signals that a cell is proliferating, while its absence indicates a cell is resting. While expressed during division, recent studies suggest Ki67 also plays functional roles, such as organizing genetic material. During mitosis, Ki67 coats the chromosomes and acts like a biological surfactant, preventing them from clumping together.
This function helps ensure that chromosomes can be properly aligned and segregated into the two new cells. In the periods between division (interphase), Ki67 is also involved in organizing heterochromatin, a tightly packed form of DNA. These roles in maintaining nuclear architecture are distinct from its utility as a proliferation marker.
Measuring Cellular Proliferation
Pathologists measure Ki67 in a tumor sample to determine the fraction of its cells that are actively dividing. The standard technique is immunohistochemistry (IHC). This method involves applying a solution with specific antibodies to a thin slice of tumor tissue. These antibodies are designed to recognize and bind only to the Ki67 protein.
Once the antibodies attach to any Ki67 protein, a chemical reaction creates a visible stain. As a result, the nucleus of any cell that was actively dividing will appear stained under a microscope. Resting cells remain unstained.
The final step is calculating the Ki67 proliferation index, or Ki67 score. A pathologist examines the stained slide and counts the number of tumor cells with stained nuclei. This number is divided by the total number of tumor cells counted and multiplied by 100 to yield a percentage. For example, if 25 stained cells are found in a field of 100 tumor cells, the Ki67 score is 25%.
Interpreting the Ki67 Score
The Ki67 score provides a measure of the growth fraction of a tumor. A low score signifies that a small percentage of cancer cells are dividing. This indicates a slow-growing, less aggressive tumor that is likely to grow and spread at a slower pace, often resulting in a more favorable prognosis.
Conversely, a high Ki67 score indicates a large fraction of tumor cells are actively dividing. This points to a rapidly growing and more aggressive cancer. A high proliferation rate is associated with a greater likelihood of metastasis and a worse overall prognosis, as the tumor can increase in size more quickly.
The thresholds for what constitutes a “low” or “high” Ki67 score are not universal. These cutoff points vary significantly depending on the specific type of cancer being evaluated. For example, a 20% score might be considered high for one tumor but intermediate for another. Professional organizations provide guidelines for different cancers to help standardize interpretation.
Clinical Significance in Oncology
The Ki67 score influences both prognosis and treatment planning. As a prognostic tool, the score helps predict the likely course of a disease. For many cancers, including those of the breast, lung, and central nervous system, a higher Ki67 index is correlated with poorer outcomes and is considered an independent prognostic factor.
The Ki67 score also provides predictive information to guide therapeutic decisions. Many chemotherapy drugs work by targeting rapidly dividing cells. A tumor with a high Ki67 score is therefore more likely to be sensitive to these treatments, which can lead to a better response.
In breast cancer, the Ki67 score helps make decisions about chemotherapy. For patients with hormone receptor-positive tumors, a high score may lead oncologists to recommend adding chemotherapy to endocrine therapy to reduce recurrence risk. In contrast, a very low score might suggest chemotherapy would offer little benefit, helping to tailor treatment to a tumor’s specific characteristics.